Drug Interactions between fluconazole and sparsentan

If you are taking sparsentan you should avoid potassium-containing salt substitutes or over-the-counter potassium supplements without first talking to your doctor. This can cause high levels of potassium in your blood. High levels of potassium can cause weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs. Call your doctor at once if you have any of these symptoms.

Consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit should be avoided during treatment with sparsentan as they may increase the blood levels of sparsentan. This may increase the risk of side effects such as hepatotoxicity, acute kidney injury, hyperkalemia, edema, and hypotension.

Swallow sparsentan whole with water before your morning or evening meal. Take your dose with the same meal each day. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Endothelin receptor antagonists (ERAs) have been associated with aminotransferase elevations, hepatotoxicity, and cases of liver failure. Hepatic function should be assessed before treatment initiation and closely monitored during treatment. Therapy should be discontinued if aminotransferase elevations are accompanied by increases in bilirubin, or clinical symptoms of hepatotoxicity such as nausea, vomiting, fever, abdominal pain or jaundice. Treatment should be avoided in patients with elevated aminotransferases at baseline as monitoring for hepatotoxicity may be more difficult. In general, the use of ERAs is not recommended for patients with moderate to severe hepatic impairment.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Peripheral edema and fluid retention are known clinical consequences of pulmonary hypertension and also known effects of endothelin receptor antagonists. Caution and monitoring is recommended if these agents are used in patients with underlying left ventricular dysfunction or underlying heart failure, as they have an increased risk for developing significant fluid retention that may need treatment or require discontinuation.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Sparsentan is associated with a risk of renal impairment, including acute kidney injury, and hyperkalemia. Patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion may be at particular risk of developing acute kidney injury or hyperkalemia. Use caution and monitor renal function closely.